Mary Ann Moon

Coronary artery bypass grafting was more effective at relieving angina, and required fewer repeat revascularization procedures, than did percutaneous coronary interventions, according to investigators who conducted a review of randomized clinical trials reported in the literature.

Neither procedural survival nor long-term survival differed significantly between CABG and PCI, but the short-term risk for stroke was significantly higher for CABG, the researchers said.

Dr. Dena M. Bravata and her associates at Stanford (Calif.) University's center for primary care and outcomes research reviewed 23 randomized trials that directly compared the effectiveness of the two approaches to revascularization. The trials included nearly 10,000 subjects in whom both procedures were technically feasible (5,019 randomly assigned to undergo PCI and 4,944 assigned to CABG). Most of the studies took place in Europe.

The rate of procedure-related stroke, reported in 15 of the trials, was higher for CABG (1.2%) than for PCI (0.6%).

Follow-up in the clinical trials ranged from 6 months to 13 years. Long-term survival was not significantly different at any time point: 96.4% for CABG and 96.5% for PCI at 1 year; 90.7% and 89.7%, respectively, at 5 years.

Angina relief was superior for CABG. At 1 year, 84% of CABG patients, compared with 75% of PCI patients, were free of angina. At 5 years, the proportions were 84% and 79%, respectively.

PCI patients were 24% more likely to require repeat revascularization (26% at 1 year and 40% at 5 years), compared with CABG patients (4% at 1 year and 10% at 5 years).

The review's finding of similar long-term survival for CABG and PCI differ from reports based on clinical registries, which show improved survival after CABG, the investigators noted. “These observations suggest that the seemingly disparate results of randomized trials and clinical registries can be reconciled by taking into account that the overall outcomes in clinical registries are heavily weighted by the large number of events in the higher-risk patients with the most extensive disease, who appear to have better outcomes after CABG than after PCI.” By contrast, overall outcomes in the randomized trials “were assessed in intermediate-risk patients, in whom CABG and PCI outcomes were also similar in clinical registries,” they explained.

ELSEVIER GLOBAL MEDICAL NEWS

Coronary artery bypass grafting was more effective at relieving angina, and required fewer repeat revascularization procedures, than did percutaneous coronary interventions, according to investigators who conducted a review of randomized clinical trials reported in the literature.

Neither procedural survival nor long-term survival differed significantly between CABG and PCI, but the short-term risk for stroke was significantly higher for CABG, the researchers said.

Dr. Dena M. Bravata and her associates at Stanford (Calif.) University's center for primary care and outcomes research reviewed 23 randomized trials that directly compared the effectiveness of the two approaches to revascularization. The trials included nearly 10,000 subjects in whom both procedures were technically feasible (5,019 randomly assigned to undergo PCI and 4,944 assigned to CABG). Most of the studies took place in Europe.

The rate of procedure-related stroke, reported in 15 of the trials, was higher for CABG (1.2%) than for PCI (0.6%).

Follow-up in the clinical trials ranged from 6 months to 13 years. Long-term survival was not significantly different at any time point: 96.4% for CABG and 96.5% for PCI at 1 year; 90.7% and 89.7%, respectively, at 5 years.

Angina relief was superior for CABG. At 1 year, 84% of CABG patients, compared with 75% of PCI patients, were free of angina. At 5 years, the proportions were 84% and 79%, respectively.

PCI patients were 24% more likely to require repeat revascularization (26% at 1 year and 40% at 5 years), compared with CABG patients (4% at 1 year and 10% at 5 years).

The review's finding of similar long-term survival for CABG and PCI differ from reports based on clinical registries, which show improved survival after CABG, the investigators noted. “These observations suggest that the seemingly disparate results of randomized trials and clinical registries can be reconciled by taking into account that the overall outcomes in clinical registries are heavily weighted by the large number of events in the higher-risk patients with the most extensive disease, who appear to have better outcomes after CABG than after PCI.” By contrast, overall outcomes in the randomized trials “were assessed in intermediate-risk patients, in whom CABG and PCI outcomes were also similar in clinical registries,” they explained.

ELSEVIER GLOBAL MEDICAL NEWS

Coronary artery bypass grafting was more effective at relieving angina, and required fewer repeat revascularization procedures, than did percutaneous coronary interventions, according to investigators who conducted a review of randomized clinical trials reported in the literature.

Neither procedural survival nor long-term survival differed significantly between CABG and PCI, but the short-term risk for stroke was significantly higher for CABG, the researchers said.

Dr. Dena M. Bravata and her associates at Stanford (Calif.) University's center for primary care and outcomes research reviewed 23 randomized trials that directly compared the effectiveness of the two approaches to revascularization. The trials included nearly 10,000 subjects in whom both procedures were technically feasible (5,019 randomly assigned to undergo PCI and 4,944 assigned to CABG). Most of the studies took place in Europe.

The rate of procedure-related stroke, reported in 15 of the trials, was higher for CABG (1.2%) than for PCI (0.6%).

Follow-up in the clinical trials ranged from 6 months to 13 years. Long-term survival was not significantly different at any time point: 96.4% for CABG and 96.5% for PCI at 1 year; 90.7% and 89.7%, respectively, at 5 years.

Angina relief was superior for CABG. At 1 year, 84% of CABG patients, compared with 75% of PCI patients, were free of angina. At 5 years, the proportions were 84% and 79%, respectively.

PCI patients were 24% more likely to require repeat revascularization (26% at 1 year and 40% at 5 years), compared with CABG patients (4% at 1 year and 10% at 5 years).

The review's finding of similar long-term survival for CABG and PCI differ from reports based on clinical registries, which show improved survival after CABG, the investigators noted. “These observations suggest that the seemingly disparate results of randomized trials and clinical registries can be reconciled by taking into account that the overall outcomes in clinical registries are heavily weighted by the large number of events in the higher-risk patients with the most extensive disease, who appear to have better outcomes after CABG than after PCI.” By contrast, overall outcomes in the randomized trials “were assessed in intermediate-risk patients, in whom CABG and PCI outcomes were also similar in clinical registries,” they explained.

ELSEVIER GLOBAL MEDICAL NEWS

Colon cancer patients who eat a typical Western diet appear to have triple the risk of recurrence, compared with those who do not follow a Western diet.

After a potentially curative resection of stage III colon cancer and adjuvant chemotherapy, a diet replete with sweets, french fries, refined grains, and red and processed meats “may facilitate a milieu that allows residual microscopic disease to proliferate and spread,” Dr. Jeffrey A. Meyerhardt of the Dana-Farber Cancer Institute, Boston, and his associates said.

Numerous studies have examined the influence of diet and other lifestyle factors on the development of colon cancer, but few have addressed diet's influence in patients with established colon cancer. Dr. Meyerhardt and his associates assessed the effect of two distinct dietary patterns—a typical Western diet versus what the investigators termed a “prudent” diet that included greater intakes of fruits, vegetables, legumes, fish, poultry, and whole grains—in 1,009 adult subjects who were already participating in a National Cancer Institute trial comparing different chemotherapy regimens.

The subjects had undergone complete surgical resection of the primary tumor in 1999–2001, and were found to have regional lymph node metastases but no distant metastases. Their diets were assessed midway through the course of adjuvant chemotherapy. The patients were followed for a median of 5 years; a total of 324 developed a recurrence during follow-up.

Greater intake of a Western diet was associated with recurrence and with cancer mortality. Patients in the highest quintile of the Western dietary pattern were three times more likely to develop recurrence and to die from cancer than were those in the lowest quintile of the Western dietary pattern, Dr. Meyerhardt and his associates said (JAMA 2007;298:754–64).

In contrast, there was no association between the prudent diet and risk of cancer recurrence or cancer mortality.

ELSEVIER GLOBAL MEDICAL NEWS

Colon cancer patients who eat a typical Western diet appear to have triple the risk of recurrence, compared with those who do not follow a Western diet.

After a potentially curative resection of stage III colon cancer and adjuvant chemotherapy, a diet replete with sweets, french fries, refined grains, and red and processed meats “may facilitate a milieu that allows residual microscopic disease to proliferate and spread,” Dr. Jeffrey A. Meyerhardt of the Dana-Farber Cancer Institute, Boston, and his associates said.

Numerous studies have examined the influence of diet and other lifestyle factors on the development of colon cancer, but few have addressed diet's influence in patients with established colon cancer. Dr. Meyerhardt and his associates assessed the effect of two distinct dietary patterns—a typical Western diet versus what the investigators termed a “prudent” diet that included greater intakes of fruits, vegetables, legumes, fish, poultry, and whole grains—in 1,009 adult subjects who were already participating in a National Cancer Institute trial comparing different chemotherapy regimens.

The subjects had undergone complete surgical resection of the primary tumor in 1999–2001, and were found to have regional lymph node metastases but no distant metastases. Their diets were assessed midway through the course of adjuvant chemotherapy. The patients were followed for a median of 5 years; a total of 324 developed a recurrence during follow-up.

Greater intake of a Western diet was associated with recurrence and with cancer mortality. Patients in the highest quintile of the Western dietary pattern were three times more likely to develop recurrence and to die from cancer than were those in the lowest quintile of the Western dietary pattern, Dr. Meyerhardt and his associates said (JAMA 2007;298:754–64).

In contrast, there was no association between the prudent diet and risk of cancer recurrence or cancer mortality.

ELSEVIER GLOBAL MEDICAL NEWS

Colon cancer patients who eat a typical Western diet appear to have triple the risk of recurrence, compared with those who do not follow a Western diet.

After a potentially curative resection of stage III colon cancer and adjuvant chemotherapy, a diet replete with sweets, french fries, refined grains, and red and processed meats “may facilitate a milieu that allows residual microscopic disease to proliferate and spread,” Dr. Jeffrey A. Meyerhardt of the Dana-Farber Cancer Institute, Boston, and his associates said.

Numerous studies have examined the influence of diet and other lifestyle factors on the development of colon cancer, but few have addressed diet's influence in patients with established colon cancer. Dr. Meyerhardt and his associates assessed the effect of two distinct dietary patterns—a typical Western diet versus what the investigators termed a “prudent” diet that included greater intakes of fruits, vegetables, legumes, fish, poultry, and whole grains—in 1,009 adult subjects who were already participating in a National Cancer Institute trial comparing different chemotherapy regimens.

The subjects had undergone complete surgical resection of the primary tumor in 1999–2001, and were found to have regional lymph node metastases but no distant metastases. Their diets were assessed midway through the course of adjuvant chemotherapy. The patients were followed for a median of 5 years; a total of 324 developed a recurrence during follow-up.

Greater intake of a Western diet was associated with recurrence and with cancer mortality. Patients in the highest quintile of the Western dietary pattern were three times more likely to develop recurrence and to die from cancer than were those in the lowest quintile of the Western dietary pattern, Dr. Meyerhardt and his associates said (JAMA 2007;298:754–64).

In contrast, there was no association between the prudent diet and risk of cancer recurrence or cancer mortality.

ELSEVIER GLOBAL MEDICAL NEWS

An annual infusion of zoledronic acid reduced the rate of new clinical fractures and improved survival in patients who had recently undergone surgical repair of a hip fracture, according to Dr. Kenneth W. Lyles and associates in the HORIZON Recurrent Fracture Trial.

The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study, supported by Novartis, is an international clinical trial that directly compared the potent bisphosphonate with placebo in 2,127 patients who were followed for a mean of 2 years, the investigators reported in a Sept. 17 posting on the New England Journal of Medicine Web site.

“It is noteworthy that no other controlled clinical trial has previously shown efficacy of any osteoporosis medication for reducing the recurrence of fracture in patients who already had a broken hip,” Dr. Karim Calis and Dr. Frank Pucino said in an editorial comment accompanying the HORIZON investigators' report.

All of the study subjects had sustained a hip fracture after minimal trauma and had undergone surgical repair, then received their first intravenous infusion within 90 days. They also received daily oral calcium and vitamin D supplements, and were allowed to have concomitant therapy with nasal calcitonin, selective estrogen receptor modulators (SERMs), hormone therapy, tibolone, or external hip protectors.

A total of 1,065 patients were randomly assigned to receive IV zoledronic acid and 1,062 to receive IV placebo once yearly. All the subjects were either intolerant of oral bisphosphonates or refused to take them. Mean patient age was 74 years.

A total of 424 new clinical fractures occurred during follow-up. The rate was 8.6% with zoledronic acid and 13.9% with placebo. Zoledronic acid thus significantly reduced the relative risk of a new clinical fracture by 35%, said Dr. Lyles of Duke University Medical Center, Durham, N.C., and his associates.

A total of 242 subjects died during follow-up. Mortality was 9.6% with zoledronic acid and 13.3% with placebo, for a significant 28% reduction in relative risk.

Bone mineral density at the hip increased 2.6% at 1 year, 4.7% at 2 years, and 5.5% at 3 years in the group receiving zoledronic acid. In contrast, it declined in the placebo group 1.0%, 0.7%, and 0.9%, respectively.

Similarly, bone mineral density at the femoral neck increased 0.8%, 2.2%, and 3.6% in the zoledronic acid group, while it declined in the placebo group 1.0%, 0.7%, and 0.9%. All of these differences were significant, the investigators said (N. Engl. J. Med. 2007 Sept. 17 [Epub doi:10.1056/NEJMoa074941]).

The rates of overall adverse events and serious adverse events were similar in the two groups. There were no differences in the frequencies of cardiovascular adverse effects nor in rates of renal toxic effects, even though the incidence of mild to moderate kidney disease was high at baseline.

There were no cases of osteonecrosis of the jaw, which previous research has suggested might be associated with zoledronic acid. Similarly, despite some concern that the drug might impair fracture healing, there was no evidence of delayed union of fractured bone in those who took it.

In their editorial comment, Dr. Calis and Dr. Pucino, both of the National Institutes of Health, Bethesda, Md., termed the study results “powerful and compelling.”

“The reduction in fracture incidence and death was striking and clearly establishes the need for pharmacologic intervention in patients who fracture a hip,” they noted (N. Engl. J. Med. 2007 Sept. 17 [Epub10.10565/NEJMe078192]).

ELSEVIER GLOBAL MEDICAL NEWS

An annual infusion of zoledronic acid reduced the rate of new clinical fractures and improved survival in patients who had recently undergone surgical repair of a hip fracture, according to Dr. Kenneth W. Lyles and associates in the HORIZON Recurrent Fracture Trial.

The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study, supported by Novartis, is an international clinical trial that directly compared the potent bisphosphonate with placebo in 2,127 patients who were followed for a mean of 2 years, the investigators reported in a Sept. 17 posting on the New England Journal of Medicine Web site.

“It is noteworthy that no other controlled clinical trial has previously shown efficacy of any osteoporosis medication for reducing the recurrence of fracture in patients who already had a broken hip,” Dr. Karim Calis and Dr. Frank Pucino said in an editorial comment accompanying the HORIZON investigators' report.

All of the study subjects had sustained a hip fracture after minimal trauma and had undergone surgical repair, then received their first intravenous infusion within 90 days. They also received daily oral calcium and vitamin D supplements, and were allowed to have concomitant therapy with nasal calcitonin, selective estrogen receptor modulators (SERMs), hormone therapy, tibolone, or external hip protectors.

A total of 1,065 patients were randomly assigned to receive IV zoledronic acid and 1,062 to receive IV placebo once yearly. All the subjects were either intolerant of oral bisphosphonates or refused to take them. Mean patient age was 74 years.

A total of 424 new clinical fractures occurred during follow-up. The rate was 8.6% with zoledronic acid and 13.9% with placebo. Zoledronic acid thus significantly reduced the relative risk of a new clinical fracture by 35%, said Dr. Lyles of Duke University Medical Center, Durham, N.C., and his associates.

A total of 242 subjects died during follow-up. Mortality was 9.6% with zoledronic acid and 13.3% with placebo, for a significant 28% reduction in relative risk.

Bone mineral density at the hip increased 2.6% at 1 year, 4.7% at 2 years, and 5.5% at 3 years in the group receiving zoledronic acid. In contrast, it declined in the placebo group 1.0%, 0.7%, and 0.9%, respectively.

Similarly, bone mineral density at the femoral neck increased 0.8%, 2.2%, and 3.6% in the zoledronic acid group, while it declined in the placebo group 1.0%, 0.7%, and 0.9%. All of these differences were significant, the investigators said (N. Engl. J. Med. 2007 Sept. 17 [Epub doi:10.1056/NEJMoa074941]).

The rates of overall adverse events and serious adverse events were similar in the two groups. There were no differences in the frequencies of cardiovascular adverse effects nor in rates of renal toxic effects, even though the incidence of mild to moderate kidney disease was high at baseline.

There were no cases of osteonecrosis of the jaw, which previous research has suggested might be associated with zoledronic acid. Similarly, despite some concern that the drug might impair fracture healing, there was no evidence of delayed union of fractured bone in those who took it.

In their editorial comment, Dr. Calis and Dr. Pucino, both of the National Institutes of Health, Bethesda, Md., termed the study results “powerful and compelling.”

“The reduction in fracture incidence and death was striking and clearly establishes the need for pharmacologic intervention in patients who fracture a hip,” they noted (N. Engl. J. Med. 2007 Sept. 17 [Epub10.10565/NEJMe078192]).

ELSEVIER GLOBAL MEDICAL NEWS

An annual infusion of zoledronic acid reduced the rate of new clinical fractures and improved survival in patients who had recently undergone surgical repair of a hip fracture, according to Dr. Kenneth W. Lyles and associates in the HORIZON Recurrent Fracture Trial.

The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study, supported by Novartis, is an international clinical trial that directly compared the potent bisphosphonate with placebo in 2,127 patients who were followed for a mean of 2 years, the investigators reported in a Sept. 17 posting on the New England Journal of Medicine Web site.

“It is noteworthy that no other controlled clinical trial has previously shown efficacy of any osteoporosis medication for reducing the recurrence of fracture in patients who already had a broken hip,” Dr. Karim Calis and Dr. Frank Pucino said in an editorial comment accompanying the HORIZON investigators' report.

All of the study subjects had sustained a hip fracture after minimal trauma and had undergone surgical repair, then received their first intravenous infusion within 90 days. They also received daily oral calcium and vitamin D supplements, and were allowed to have concomitant therapy with nasal calcitonin, selective estrogen receptor modulators (SERMs), hormone therapy, tibolone, or external hip protectors.

A total of 1,065 patients were randomly assigned to receive IV zoledronic acid and 1,062 to receive IV placebo once yearly. All the subjects were either intolerant of oral bisphosphonates or refused to take them. Mean patient age was 74 years.

A total of 424 new clinical fractures occurred during follow-up. The rate was 8.6% with zoledronic acid and 13.9% with placebo. Zoledronic acid thus significantly reduced the relative risk of a new clinical fracture by 35%, said Dr. Lyles of Duke University Medical Center, Durham, N.C., and his associates.

A total of 242 subjects died during follow-up. Mortality was 9.6% with zoledronic acid and 13.3% with placebo, for a significant 28% reduction in relative risk.

Bone mineral density at the hip increased 2.6% at 1 year, 4.7% at 2 years, and 5.5% at 3 years in the group receiving zoledronic acid. In contrast, it declined in the placebo group 1.0%, 0.7%, and 0.9%, respectively.

Similarly, bone mineral density at the femoral neck increased 0.8%, 2.2%, and 3.6% in the zoledronic acid group, while it declined in the placebo group 1.0%, 0.7%, and 0.9%. All of these differences were significant, the investigators said (N. Engl. J. Med. 2007 Sept. 17 [Epub doi:10.1056/NEJMoa074941]).

The rates of overall adverse events and serious adverse events were similar in the two groups. There were no differences in the frequencies of cardiovascular adverse effects nor in rates of renal toxic effects, even though the incidence of mild to moderate kidney disease was high at baseline.

There were no cases of osteonecrosis of the jaw, which previous research has suggested might be associated with zoledronic acid. Similarly, despite some concern that the drug might impair fracture healing, there was no evidence of delayed union of fractured bone in those who took it.

In their editorial comment, Dr. Calis and Dr. Pucino, both of the National Institutes of Health, Bethesda, Md., termed the study results “powerful and compelling.”

“The reduction in fracture incidence and death was striking and clearly establishes the need for pharmacologic intervention in patients who fracture a hip,” they noted (N. Engl. J. Med. 2007 Sept. 17 [Epub10.10565/NEJMe078192]).

ELSEVIER GLOBAL MEDICAL NEWS

Colorectal neoplasms are nearly twice as common in patients newly diagnosed as having coronary artery disease than in those found not to have CAD based on coronary angiography, results of a cross-sectional study suggest.

The prevalence of colorectal neoplasms in patients with CAD in their study was nearly three times as high as that reported in the general population in either Hong Kong or the United States, investigators reported.

Dr. Annie On On Chan of the University of Hong Kong and her associates previously published a retrospective study showing a strong association between colorectal neoplasms and CAD. To further examine this link, they conducted a cross-sectional study of consecutive patients who were undergoing coronary angiography to assess suspected CAD, followed by colonoscopy.

In industrialized Hong Kong, incidence rates of colorectal cancer and CAD, and mortality from the conditions, are similar to the rates in Western countries, they noted.

The study included 206 patients who were found to have CAD, 208 patients who were found not to have CAD, and a control group of 207 people from the general Hong Kong population who were matched to the other subjects based on age and sex. The family histories of colorectal cancer were similar among the three groups.

Colonoscopy revealed that colorectal neoplasms were more prevalent in the CAD-positive group (34%) than in the CAD-negative group (18%) or the control group (20%).

This 34% prevalence in patients newly diagnosed as having CAD was especially “remarkable,” compared with the current prevalences reported in the general population in Hong Kong (12%) and the United States (10%), Dr. Chan and her associates said (JAMA 2007;298:1412–9).

Similarly, the prevalences of advanced colorectal lesions and adenocarcinomas were much higher in the patients with CAD (18% and 4%, respectively) than in the patients who didn't have CAD (6% and 0.5%) or the control subjects (5% and 1%).

The reason for this association between CAD and colorectal neoplasm is not yet known, but it is possible that the two disorders share common environmental risk factors. Moreover, both disorders have been linked to metabolic syndrome and smoking, and both “probably develop through the mechanism of chronic inflammation,” the investigators said.

ELSEVIER GLOBAL MEDICAL NEWS

Colorectal neoplasms are nearly twice as common in patients newly diagnosed as having coronary artery disease than in those found not to have CAD based on coronary angiography, results of a cross-sectional study suggest.

The prevalence of colorectal neoplasms in patients with CAD in their study was nearly three times as high as that reported in the general population in either Hong Kong or the United States, investigators reported.

Dr. Annie On On Chan of the University of Hong Kong and her associates previously published a retrospective study showing a strong association between colorectal neoplasms and CAD. To further examine this link, they conducted a cross-sectional study of consecutive patients who were undergoing coronary angiography to assess suspected CAD, followed by colonoscopy.

In industrialized Hong Kong, incidence rates of colorectal cancer and CAD, and mortality from the conditions, are similar to the rates in Western countries, they noted.

The study included 206 patients who were found to have CAD, 208 patients who were found not to have CAD, and a control group of 207 people from the general Hong Kong population who were matched to the other subjects based on age and sex. The family histories of colorectal cancer were similar among the three groups.

Colonoscopy revealed that colorectal neoplasms were more prevalent in the CAD-positive group (34%) than in the CAD-negative group (18%) or the control group (20%).

This 34% prevalence in patients newly diagnosed as having CAD was especially “remarkable,” compared with the current prevalences reported in the general population in Hong Kong (12%) and the United States (10%), Dr. Chan and her associates said (JAMA 2007;298:1412–9).

Similarly, the prevalences of advanced colorectal lesions and adenocarcinomas were much higher in the patients with CAD (18% and 4%, respectively) than in the patients who didn't have CAD (6% and 0.5%) or the control subjects (5% and 1%).

The reason for this association between CAD and colorectal neoplasm is not yet known, but it is possible that the two disorders share common environmental risk factors. Moreover, both disorders have been linked to metabolic syndrome and smoking, and both “probably develop through the mechanism of chronic inflammation,” the investigators said.

ELSEVIER GLOBAL MEDICAL NEWS

Colorectal neoplasms are nearly twice as common in patients newly diagnosed as having coronary artery disease than in those found not to have CAD based on coronary angiography, results of a cross-sectional study suggest.

The prevalence of colorectal neoplasms in patients with CAD in their study was nearly three times as high as that reported in the general population in either Hong Kong or the United States, investigators reported.

Dr. Annie On On Chan of the University of Hong Kong and her associates previously published a retrospective study showing a strong association between colorectal neoplasms and CAD. To further examine this link, they conducted a cross-sectional study of consecutive patients who were undergoing coronary angiography to assess suspected CAD, followed by colonoscopy.

In industrialized Hong Kong, incidence rates of colorectal cancer and CAD, and mortality from the conditions, are similar to the rates in Western countries, they noted.

The study included 206 patients who were found to have CAD, 208 patients who were found not to have CAD, and a control group of 207 people from the general Hong Kong population who were matched to the other subjects based on age and sex. The family histories of colorectal cancer were similar among the three groups.

Colonoscopy revealed that colorectal neoplasms were more prevalent in the CAD-positive group (34%) than in the CAD-negative group (18%) or the control group (20%).

This 34% prevalence in patients newly diagnosed as having CAD was especially “remarkable,” compared with the current prevalences reported in the general population in Hong Kong (12%) and the United States (10%), Dr. Chan and her associates said (JAMA 2007;298:1412–9).

Similarly, the prevalences of advanced colorectal lesions and adenocarcinomas were much higher in the patients with CAD (18% and 4%, respectively) than in the patients who didn't have CAD (6% and 0.5%) or the control subjects (5% and 1%).

The reason for this association between CAD and colorectal neoplasm is not yet known, but it is possible that the two disorders share common environmental risk factors. Moreover, both disorders have been linked to metabolic syndrome and smoking, and both “probably develop through the mechanism of chronic inflammation,” the investigators said.

ELSEVIER GLOBAL MEDICAL NEWS

Pioglitazone appears to lower the risk of death, myocardial infarction, and stroke in diabetes patients, just the opposite of the closely related drug rosiglitazone, according to separate meta-analyses on the two agents.

It is not yet clear why these two thiazolidinediones may have such disparate effects on cardiovascular outcomes, the investigators said.

In one meta-analysis, Dr. A. Michael Lincoff and his associates at the Cleveland Clinic used data provided by Takeda Pharma, manufacturer of Actos, to assess pioglitazone's effect on the incidence of ischemic cardiovascular complications. They pooled data on 19 randomized, double-blinded, controlled clinical trials of the drug in 16,390 diabetes patients.

The investigators found that the composite outcome of death, myocardial infarction, or stroke was 18% lower in patients who took pioglitazone than in those who received placebo or other diabetes medications.

“The magnitude and direction of this protective effect … was homogeneous across trials of different durations ranging from 4 months to 3.5 years, across studies using a variety of control or concomitant diabetic therapies, and among trials of patients with and without established vascular disease,” Dr. Lincoff and his associates said (JAMA 2007;298:1180–8).

Like rosiglitazone, pioglitazone was found to raise the rate of congestive heart failure. However, it did not increase the incidence of heart failure mortality.

“These findings suggest that the net clinical cardiovascular benefit with pioglitazone therapy is favorable, with an important reduction in irreversible ischemic events that is not attenuated by the risk of more frequent heart failure complications,” Dr. Lincoff and his associates said.

In contrast, Dr. Sonal Singh of Wake Forest University, Winston-Salem, N.C., and his associates found in their meta-analysis that rosiglitazone significantly raised the risk of both myocardial infarction and heart failure.

This led them to conclude that “regulatory agencies ought to reevaluate whether rosiglitazone should be allowed to remain on the market.”

The researchers pooled the results of four randomized clinical trials of at least 1 year's duration (14,291 patients) and three systematic reviews to assess rosiglitazone's effect on MI, heart failure, and cardiovascular mortality.

The drug approximately doubled the risk of heart failure, and increased the risk of MI by 42%. However, it did not affect the risk of cardiovascular death.

“We estimate that there may be more than 3.5 million current users of rosiglitazone in the United States alone,” which may account for 4,000 excess MIs and 9,000 excess heart failure events among Americans each year, the researchers wrote (JAMA 2007;298:1189–95).

In August, the U.S. Food and Drug Administration announced that the labels of all thiazolidinediones will now carry a black box warning about the risk of heart failure.

“Health plans and physicians should not wait for regulatory actions. They should avoid using rosiglitazone in patients with diabetes who are at risk of cardiovascular events, especially since safer treatment alternatives are available,” Dr. Singh and his associates said.

Pioglitazone appears to lower the risk of death, myocardial infarction, and stroke in diabetes patients, just the opposite of the closely related drug rosiglitazone, according to separate meta-analyses on the two agents.

It is not yet clear why these two thiazolidinediones may have such disparate effects on cardiovascular outcomes, the investigators said.

In one meta-analysis, Dr. A. Michael Lincoff and his associates at the Cleveland Clinic used data provided by Takeda Pharma, manufacturer of Actos, to assess pioglitazone's effect on the incidence of ischemic cardiovascular complications. They pooled data on 19 randomized, double-blinded, controlled clinical trials of the drug in 16,390 diabetes patients.

The investigators found that the composite outcome of death, myocardial infarction, or stroke was 18% lower in patients who took pioglitazone than in those who received placebo or other diabetes medications.

“The magnitude and direction of this protective effect … was homogeneous across trials of different durations ranging from 4 months to 3.5 years, across studies using a variety of control or concomitant diabetic therapies, and among trials of patients with and without established vascular disease,” Dr. Lincoff and his associates said (JAMA 2007;298:1180–8).

Like rosiglitazone, pioglitazone was found to raise the rate of congestive heart failure. However, it did not increase the incidence of heart failure mortality.

“These findings suggest that the net clinical cardiovascular benefit with pioglitazone therapy is favorable, with an important reduction in irreversible ischemic events that is not attenuated by the risk of more frequent heart failure complications,” Dr. Lincoff and his associates said.

In contrast, Dr. Sonal Singh of Wake Forest University, Winston-Salem, N.C., and his associates found in their meta-analysis that rosiglitazone significantly raised the risk of both myocardial infarction and heart failure.

This led them to conclude that “regulatory agencies ought to reevaluate whether rosiglitazone should be allowed to remain on the market.”

The researchers pooled the results of four randomized clinical trials of at least 1 year's duration (14,291 patients) and three systematic reviews to assess rosiglitazone's effect on MI, heart failure, and cardiovascular mortality.

The drug approximately doubled the risk of heart failure, and increased the risk of MI by 42%. However, it did not affect the risk of cardiovascular death.

“We estimate that there may be more than 3.5 million current users of rosiglitazone in the United States alone,” which may account for 4,000 excess MIs and 9,000 excess heart failure events among Americans each year, the researchers wrote (JAMA 2007;298:1189–95).

In August, the U.S. Food and Drug Administration announced that the labels of all thiazolidinediones will now carry a black box warning about the risk of heart failure.

“Health plans and physicians should not wait for regulatory actions. They should avoid using rosiglitazone in patients with diabetes who are at risk of cardiovascular events, especially since safer treatment alternatives are available,” Dr. Singh and his associates said.

Pioglitazone appears to lower the risk of death, myocardial infarction, and stroke in diabetes patients, just the opposite of the closely related drug rosiglitazone, according to separate meta-analyses on the two agents.

It is not yet clear why these two thiazolidinediones may have such disparate effects on cardiovascular outcomes, the investigators said.

In one meta-analysis, Dr. A. Michael Lincoff and his associates at the Cleveland Clinic used data provided by Takeda Pharma, manufacturer of Actos, to assess pioglitazone's effect on the incidence of ischemic cardiovascular complications. They pooled data on 19 randomized, double-blinded, controlled clinical trials of the drug in 16,390 diabetes patients.

The investigators found that the composite outcome of death, myocardial infarction, or stroke was 18% lower in patients who took pioglitazone than in those who received placebo or other diabetes medications.

“The magnitude and direction of this protective effect … was homogeneous across trials of different durations ranging from 4 months to 3.5 years, across studies using a variety of control or concomitant diabetic therapies, and among trials of patients with and without established vascular disease,” Dr. Lincoff and his associates said (JAMA 2007;298:1180–8).

Like rosiglitazone, pioglitazone was found to raise the rate of congestive heart failure. However, it did not increase the incidence of heart failure mortality.

“These findings suggest that the net clinical cardiovascular benefit with pioglitazone therapy is favorable, with an important reduction in irreversible ischemic events that is not attenuated by the risk of more frequent heart failure complications,” Dr. Lincoff and his associates said.

In contrast, Dr. Sonal Singh of Wake Forest University, Winston-Salem, N.C., and his associates found in their meta-analysis that rosiglitazone significantly raised the risk of both myocardial infarction and heart failure.

This led them to conclude that “regulatory agencies ought to reevaluate whether rosiglitazone should be allowed to remain on the market.”

The researchers pooled the results of four randomized clinical trials of at least 1 year's duration (14,291 patients) and three systematic reviews to assess rosiglitazone's effect on MI, heart failure, and cardiovascular mortality.

The drug approximately doubled the risk of heart failure, and increased the risk of MI by 42%. However, it did not affect the risk of cardiovascular death.

“We estimate that there may be more than 3.5 million current users of rosiglitazone in the United States alone,” which may account for 4,000 excess MIs and 9,000 excess heart failure events among Americans each year, the researchers wrote (JAMA 2007;298:1189–95).

In August, the U.S. Food and Drug Administration announced that the labels of all thiazolidinediones will now carry a black box warning about the risk of heart failure.

“Health plans and physicians should not wait for regulatory actions. They should avoid using rosiglitazone in patients with diabetes who are at risk of cardiovascular events, especially since safer treatment alternatives are available,” Dr. Singh and his associates said.

An annual intravenous infusion of zoledronic acid reduced the rate of new clinical fractures and improved survival in patients who had recently undergone surgery for a hip fracture, according to Dr. Kenneth W. Lyles and associates in the HORIZON Recurrent Fracture Trial.

The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study, supported by Novartis, is an international clinical trial that compared the potent bisphosphonate with placebo in 2,127 patients followed for a mean of 2 years, the investigators reported on the New England Journal of Medicine Web site. “No other controlled clinical trial has previously shown efficacy of any osteoporosis medication for reducing the recurrence of fracture in patients who already had a broken hip,” Dr. Karim Calis and Dr. Frank Pucino wrote in an editorial accompanying the report.

All subjects sustained a hip fracture after minimal trauma and underwent surgical repair, then received their first intravenous infusion within 90 days. They received daily oral calcium and vitamin D supplements, and were allowed concomitant therapy with nasal calcitonin, selective estrogen receptor modulators, hormone therapy, tibolone, or external hip protectors. A total of 1,065 patients were randomly assigned to IV zoledronic acid and 1,062 to IV placebo once yearly. Mean age was 74 years.

A total of 424 new clinical fractures occurred during follow-up. The rate was 8.6% with zoledronic acid and 13.9% with placebo, for a reduction in relative risk of 35%, said Dr. Lyles, of Duke University Medical Center, Durham, N.C. A total of 242 subjects died. Mortality was 9.6% with zoledronic acid and 13.3% with placebo, for a significant 28% relative risk reduction.

Bone mineral density (BMD) at the hip increased 2.6% at 1 year, 4.7% at 2 years, and 5.5% at 3 years in the zoledronic acid group. In the placebo group it fell 1.0%, 0.7%, and 0.9%, respectively. BMD at the femoral neck increased 0.8%, 2.2%, and 3.6% in the zoledronic acid group. It declined in the placebo group 1.0%, 0.7%, and 0.9%. All differences were significant (N. Engl. J. Med. 2007 Sept. 17 [Epub doi:10.1056/NEJMoa074941]).

Rates of overall adverse events and serious adverse events were similar. There were no differences in frequencies of cardiovascular adverse effects nor in rates of renal toxic effects. There were no cases of osteonecrosis of the jaw, which research suggested might be tied to zoledronic acid. There was no evidence of delayed bone healing, either.

In their comment, Dr. Calis and Dr. Pucino, both of the National Institutes of Health, Bethesda, Md., wrote, “Zoledronic acid appears to offer several advantages over other potential therapies, with one important caveat: Although the risk-benefit pendulum has now swung in favor of treatment, additional long-term safety data are essential,” (N. Engl. J. Med. 2007 Sept. 17 [Epub10.10565/N EJMe078192]). Future studies should compare treatment with other therapies and address physical function, quality of life, and cost-effectiveness, they added.

ELSEVIER GLOBAL MEDICAL NEWS

An annual intravenous infusion of zoledronic acid reduced the rate of new clinical fractures and improved survival in patients who had recently undergone surgery for a hip fracture, according to Dr. Kenneth W. Lyles and associates in the HORIZON Recurrent Fracture Trial.

The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study, supported by Novartis, is an international clinical trial that compared the potent bisphosphonate with placebo in 2,127 patients followed for a mean of 2 years, the investigators reported on the New England Journal of Medicine Web site. “No other controlled clinical trial has previously shown efficacy of any osteoporosis medication for reducing the recurrence of fracture in patients who already had a broken hip,” Dr. Karim Calis and Dr. Frank Pucino wrote in an editorial accompanying the report.

All subjects sustained a hip fracture after minimal trauma and underwent surgical repair, then received their first intravenous infusion within 90 days. They received daily oral calcium and vitamin D supplements, and were allowed concomitant therapy with nasal calcitonin, selective estrogen receptor modulators, hormone therapy, tibolone, or external hip protectors. A total of 1,065 patients were randomly assigned to IV zoledronic acid and 1,062 to IV placebo once yearly. Mean age was 74 years.

A total of 424 new clinical fractures occurred during follow-up. The rate was 8.6% with zoledronic acid and 13.9% with placebo, for a reduction in relative risk of 35%, said Dr. Lyles, of Duke University Medical Center, Durham, N.C. A total of 242 subjects died. Mortality was 9.6% with zoledronic acid and 13.3% with placebo, for a significant 28% relative risk reduction.

Bone mineral density (BMD) at the hip increased 2.6% at 1 year, 4.7% at 2 years, and 5.5% at 3 years in the zoledronic acid group. In the placebo group it fell 1.0%, 0.7%, and 0.9%, respectively. BMD at the femoral neck increased 0.8%, 2.2%, and 3.6% in the zoledronic acid group. It declined in the placebo group 1.0%, 0.7%, and 0.9%. All differences were significant (N. Engl. J. Med. 2007 Sept. 17 [Epub doi:10.1056/NEJMoa074941]).

Rates of overall adverse events and serious adverse events were similar. There were no differences in frequencies of cardiovascular adverse effects nor in rates of renal toxic effects. There were no cases of osteonecrosis of the jaw, which research suggested might be tied to zoledronic acid. There was no evidence of delayed bone healing, either.

In their comment, Dr. Calis and Dr. Pucino, both of the National Institutes of Health, Bethesda, Md., wrote, “Zoledronic acid appears to offer several advantages over other potential therapies, with one important caveat: Although the risk-benefit pendulum has now swung in favor of treatment, additional long-term safety data are essential,” (N. Engl. J. Med. 2007 Sept. 17 [Epub10.10565/N EJMe078192]). Future studies should compare treatment with other therapies and address physical function, quality of life, and cost-effectiveness, they added.

ELSEVIER GLOBAL MEDICAL NEWS

An annual intravenous infusion of zoledronic acid reduced the rate of new clinical fractures and improved survival in patients who had recently undergone surgery for a hip fracture, according to Dr. Kenneth W. Lyles and associates in the HORIZON Recurrent Fracture Trial.

The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study, supported by Novartis, is an international clinical trial that compared the potent bisphosphonate with placebo in 2,127 patients followed for a mean of 2 years, the investigators reported on the New England Journal of Medicine Web site. “No other controlled clinical trial has previously shown efficacy of any osteoporosis medication for reducing the recurrence of fracture in patients who already had a broken hip,” Dr. Karim Calis and Dr. Frank Pucino wrote in an editorial accompanying the report.

All subjects sustained a hip fracture after minimal trauma and underwent surgical repair, then received their first intravenous infusion within 90 days. They received daily oral calcium and vitamin D supplements, and were allowed concomitant therapy with nasal calcitonin, selective estrogen receptor modulators, hormone therapy, tibolone, or external hip protectors. A total of 1,065 patients were randomly assigned to IV zoledronic acid and 1,062 to IV placebo once yearly. Mean age was 74 years.

A total of 424 new clinical fractures occurred during follow-up. The rate was 8.6% with zoledronic acid and 13.9% with placebo, for a reduction in relative risk of 35%, said Dr. Lyles, of Duke University Medical Center, Durham, N.C. A total of 242 subjects died. Mortality was 9.6% with zoledronic acid and 13.3% with placebo, for a significant 28% relative risk reduction.

Bone mineral density (BMD) at the hip increased 2.6% at 1 year, 4.7% at 2 years, and 5.5% at 3 years in the zoledronic acid group. In the placebo group it fell 1.0%, 0.7%, and 0.9%, respectively. BMD at the femoral neck increased 0.8%, 2.2%, and 3.6% in the zoledronic acid group. It declined in the placebo group 1.0%, 0.7%, and 0.9%. All differences were significant (N. Engl. J. Med. 2007 Sept. 17 [Epub doi:10.1056/NEJMoa074941]).

Rates of overall adverse events and serious adverse events were similar. There were no differences in frequencies of cardiovascular adverse effects nor in rates of renal toxic effects. There were no cases of osteonecrosis of the jaw, which research suggested might be tied to zoledronic acid. There was no evidence of delayed bone healing, either.

In their comment, Dr. Calis and Dr. Pucino, both of the National Institutes of Health, Bethesda, Md., wrote, “Zoledronic acid appears to offer several advantages over other potential therapies, with one important caveat: Although the risk-benefit pendulum has now swung in favor of treatment, additional long-term safety data are essential,” (N. Engl. J. Med. 2007 Sept. 17 [Epub10.10565/N EJMe078192]). Future studies should compare treatment with other therapies and address physical function, quality of life, and cost-effectiveness, they added.

ELSEVIER GLOBAL MEDICAL NEWS

In women who test positive for human papillomavirus DNA, the bivalent HPV-16/18 vaccination does not induce or accelerate clearance of the infection, according to a phase III study report.

Human papillomavirus (HPV) vaccination induces cell-mediated immune responses that are traditionally involved in the eradication of infection, and it has been suggested that the vaccine might benefit women who are already infected, perhaps by enhancing viral clearance. The study researchers examined the issue using a cohort drawn from a large, ongoing randomized clinical trial of vaccine efficacy.

The main study of vaccine efficacy focused on nearly 7,500 women aged 18–25 years who resided in Costa Rica, where cervical cancer screening programs incorporate HPV DNA testing with Pap tests. “Management protocols often involve retesting HPV-positive women within months of an initial HPV-positive result before treatment decisions are made, [so] understanding the impact of vaccination on viral clearance in the first 6–12 months after an initial HPV-positive result would be informative,” said Dr. Allan Hildesheim of the National Cancer Institute, Rockville, Md., and his associates (JAMA 2007;298:743–53).

They assessed viral clearance in a subset of 2,055 subjects who were positive for HPV DNA and who received either a control immunization or the bivalent HPV-16/18 vaccine that contains viruslike particles only from HPV-16 and HPV-18. This formulation has been approved for use in Australia and is under review for use in the United States and other countries.

Clearance rates for HPV-16 and/or HPV-18 were not significantly different between the active treatment and placebo treatment groups either 6 months after the initial vaccination was given (33.4% vs. 31.6%, respectively) or at 12 months, when the entire series of vaccinations was completed (48.8% vs. 49.8%).

There also was no evidence of a vaccine effect in any of several subgroups studied, including women with a particularly high viral load, women infected with only a single HPV strain, oral contraceptive users, cigarette smokers, or women with concomitant chlamydia or gonorrhea infection.

“[Our] results … provide strong evidence there is little, if any, therapeutic benefit from the vaccine,” and clinicians should discourage its use to treat existing HPV infection, the authors said.

In women who test positive for human papillomavirus DNA, the bivalent HPV-16/18 vaccination does not induce or accelerate clearance of the infection, according to a phase III study report.

Human papillomavirus (HPV) vaccination induces cell-mediated immune responses that are traditionally involved in the eradication of infection, and it has been suggested that the vaccine might benefit women who are already infected, perhaps by enhancing viral clearance. The study researchers examined the issue using a cohort drawn from a large, ongoing randomized clinical trial of vaccine efficacy.

The main study of vaccine efficacy focused on nearly 7,500 women aged 18–25 years who resided in Costa Rica, where cervical cancer screening programs incorporate HPV DNA testing with Pap tests. “Management protocols often involve retesting HPV-positive women within months of an initial HPV-positive result before treatment decisions are made, [so] understanding the impact of vaccination on viral clearance in the first 6–12 months after an initial HPV-positive result would be informative,” said Dr. Allan Hildesheim of the National Cancer Institute, Rockville, Md., and his associates (JAMA 2007;298:743–53).

They assessed viral clearance in a subset of 2,055 subjects who were positive for HPV DNA and who received either a control immunization or the bivalent HPV-16/18 vaccine that contains viruslike particles only from HPV-16 and HPV-18. This formulation has been approved for use in Australia and is under review for use in the United States and other countries.

Clearance rates for HPV-16 and/or HPV-18 were not significantly different between the active treatment and placebo treatment groups either 6 months after the initial vaccination was given (33.4% vs. 31.6%, respectively) or at 12 months, when the entire series of vaccinations was completed (48.8% vs. 49.8%).

There also was no evidence of a vaccine effect in any of several subgroups studied, including women with a particularly high viral load, women infected with only a single HPV strain, oral contraceptive users, cigarette smokers, or women with concomitant chlamydia or gonorrhea infection.

“[Our] results … provide strong evidence there is little, if any, therapeutic benefit from the vaccine,” and clinicians should discourage its use to treat existing HPV infection, the authors said.

In women who test positive for human papillomavirus DNA, the bivalent HPV-16/18 vaccination does not induce or accelerate clearance of the infection, according to a phase III study report.

Human papillomavirus (HPV) vaccination induces cell-mediated immune responses that are traditionally involved in the eradication of infection, and it has been suggested that the vaccine might benefit women who are already infected, perhaps by enhancing viral clearance. The study researchers examined the issue using a cohort drawn from a large, ongoing randomized clinical trial of vaccine efficacy.

The main study of vaccine efficacy focused on nearly 7,500 women aged 18–25 years who resided in Costa Rica, where cervical cancer screening programs incorporate HPV DNA testing with Pap tests. “Management protocols often involve retesting HPV-positive women within months of an initial HPV-positive result before treatment decisions are made, [so] understanding the impact of vaccination on viral clearance in the first 6–12 months after an initial HPV-positive result would be informative,” said Dr. Allan Hildesheim of the National Cancer Institute, Rockville, Md., and his associates (JAMA 2007;298:743–53).

They assessed viral clearance in a subset of 2,055 subjects who were positive for HPV DNA and who received either a control immunization or the bivalent HPV-16/18 vaccine that contains viruslike particles only from HPV-16 and HPV-18. This formulation has been approved for use in Australia and is under review for use in the United States and other countries.

Clearance rates for HPV-16 and/or HPV-18 were not significantly different between the active treatment and placebo treatment groups either 6 months after the initial vaccination was given (33.4% vs. 31.6%, respectively) or at 12 months, when the entire series of vaccinations was completed (48.8% vs. 49.8%).

There also was no evidence of a vaccine effect in any of several subgroups studied, including women with a particularly high viral load, women infected with only a single HPV strain, oral contraceptive users, cigarette smokers, or women with concomitant chlamydia or gonorrhea infection.

“[Our] results … provide strong evidence there is little, if any, therapeutic benefit from the vaccine,” and clinicians should discourage its use to treat existing HPV infection, the authors said.

Depression severely impairs the recovery of heart rate variability after acute coronary syndrome, reported Dr. Alexander H. Glassman of Columbia University, New York, and his associates.

In addition, heart rate variability (HRV) continues to decline in patients whose depression does not respond to sertraline (Zoloft), while it ceases to decline in those who do respond to sertraline. It is not yet known whether this cardiac benefit is attributable to a pharmacologic effect of the antidepressant, to improvement of the depressive illness, or to a combination of both, the researchers said.

“What is clear is that depression is associated with biological changes involving increased heart rate, inflammatory response, plasma norepinephrine, platelet reactivity, decreased heart rate variability, and now, absent post-ACS-HRV recovery, all of which [are] associated with life-threatening consequences,” said Dr. Glassman and his associates.

“From a clinician's point of view, patients with depression after myocardial infarction … should be both carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously,” they noted (Arch. Gen. Psychiatry 2007;64:1025–31).

The researchers used data from 258 subjects who participated in the SADHART study to examine the effects of depression and of antidepressant therapy on heart rate variability. SADHART (Sertraline Antidepressant Heart Attack Randomized Trial), which took place in 1997–2001, compared sertraline with placebo in patients with major depressive disorder who were hospitalized after ACS.

In the general population, HRV falls abruptly during acute coronary episodes and recovers gradually but incompletely in the following weeks. However, Dr. Glassman and his associates found that HRV failed to recover in ACS patients with major depression.

The decline in HRV leveled off or improved slightly in those who responded to sertraline and in those whose mood improved spontaneously, but continued to decline in patients who received placebo or who failed to respond to sertraline, the investigators said.

Even patients who responded to sertraline showed only one-third as much HRV recovery as is reported in the literature among ACS patients who do not have depression. Thus, even successful selective serotonin reuptake inhibitor therapy “may not fully eliminate the autonomic risk associated with major depressive disorder,” the investigators added.

Dr. Glassman served as a member of the steering committee for SADHART. He also has been a consultant for and has received honoraria from Pfizer Inc., which markets sertraline and provided partial support for the study.

Depression severely impairs the recovery of heart rate variability after acute coronary syndrome, reported Dr. Alexander H. Glassman of Columbia University, New York, and his associates.

In addition, heart rate variability (HRV) continues to decline in patients whose depression does not respond to sertraline (Zoloft), while it ceases to decline in those who do respond to sertraline. It is not yet known whether this cardiac benefit is attributable to a pharmacologic effect of the antidepressant, to improvement of the depressive illness, or to a combination of both, the researchers said.

“What is clear is that depression is associated with biological changes involving increased heart rate, inflammatory response, plasma norepinephrine, platelet reactivity, decreased heart rate variability, and now, absent post-ACS-HRV recovery, all of which [are] associated with life-threatening consequences,” said Dr. Glassman and his associates.

“From a clinician's point of view, patients with depression after myocardial infarction … should be both carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously,” they noted (Arch. Gen. Psychiatry 2007;64:1025–31).

The researchers used data from 258 subjects who participated in the SADHART study to examine the effects of depression and of antidepressant therapy on heart rate variability. SADHART (Sertraline Antidepressant Heart Attack Randomized Trial), which took place in 1997–2001, compared sertraline with placebo in patients with major depressive disorder who were hospitalized after ACS.

In the general population, HRV falls abruptly during acute coronary episodes and recovers gradually but incompletely in the following weeks. However, Dr. Glassman and his associates found that HRV failed to recover in ACS patients with major depression.

The decline in HRV leveled off or improved slightly in those who responded to sertraline and in those whose mood improved spontaneously, but continued to decline in patients who received placebo or who failed to respond to sertraline, the investigators said.

Even patients who responded to sertraline showed only one-third as much HRV recovery as is reported in the literature among ACS patients who do not have depression. Thus, even successful selective serotonin reuptake inhibitor therapy “may not fully eliminate the autonomic risk associated with major depressive disorder,” the investigators added.

Dr. Glassman served as a member of the steering committee for SADHART. He also has been a consultant for and has received honoraria from Pfizer Inc., which markets sertraline and provided partial support for the study.

Depression severely impairs the recovery of heart rate variability after acute coronary syndrome, reported Dr. Alexander H. Glassman of Columbia University, New York, and his associates.

In addition, heart rate variability (HRV) continues to decline in patients whose depression does not respond to sertraline (Zoloft), while it ceases to decline in those who do respond to sertraline. It is not yet known whether this cardiac benefit is attributable to a pharmacologic effect of the antidepressant, to improvement of the depressive illness, or to a combination of both, the researchers said.

“What is clear is that depression is associated with biological changes involving increased heart rate, inflammatory response, plasma norepinephrine, platelet reactivity, decreased heart rate variability, and now, absent post-ACS-HRV recovery, all of which [are] associated with life-threatening consequences,” said Dr. Glassman and his associates.

“From a clinician's point of view, patients with depression after myocardial infarction … should be both carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously,” they noted (Arch. Gen. Psychiatry 2007;64:1025–31).

The researchers used data from 258 subjects who participated in the SADHART study to examine the effects of depression and of antidepressant therapy on heart rate variability. SADHART (Sertraline Antidepressant Heart Attack Randomized Trial), which took place in 1997–2001, compared sertraline with placebo in patients with major depressive disorder who were hospitalized after ACS.

In the general population, HRV falls abruptly during acute coronary episodes and recovers gradually but incompletely in the following weeks. However, Dr. Glassman and his associates found that HRV failed to recover in ACS patients with major depression.

The decline in HRV leveled off or improved slightly in those who responded to sertraline and in those whose mood improved spontaneously, but continued to decline in patients who received placebo or who failed to respond to sertraline, the investigators said.

Even patients who responded to sertraline showed only one-third as much HRV recovery as is reported in the literature among ACS patients who do not have depression. Thus, even successful selective serotonin reuptake inhibitor therapy “may not fully eliminate the autonomic risk associated with major depressive disorder,” the investigators added.

Dr. Glassman served as a member of the steering committee for SADHART. He also has been a consultant for and has received honoraria from Pfizer Inc., which markets sertraline and provided partial support for the study.

A pooled analysis of 11 clinical studies has confirmed that cigarette smoking protects against Parkinson's disease in a dose-dependent manner.

Many studies have suggested that smoking may play a protective role in PD, but most have been too small to provide definitive answers. Dr. Beate Ritz of the University of California, Los Angeles, and associates conducted a pooled analysis of eight case-control studies and three cohort studies involving 2,816 subjects who had PD and 8,993 controls. This large data set “enabled us to investigate aspects of cigarette smoking and subgroup-specific associations that could not be addressed adequately in previous studies,” they noted.

The risk of developing PD decreased as pack-years of cigarette smoking increased, so that the average relative risk for the disease dropped 5%–8% for every 10 pack-years of smoking. This dose-response pattern was seen in both men and women, and it was not affected by subjects' educational status.

There was also a strong dose-response trend for the number of years that had elapsed since smoking cessation. Current smokers and smokers who had recently quit showed the lowest risk for PD. People who had quit smoking in the past had a higher risk for PD, but their risk was still lower than that of people who had never smoked (Arch. Neurol. 2007;64:990–7).

Two possible mechanisms for this protective effect have been proposed. Substances such as nicotine in tobacco smoke may promote the survival of dopaminergic neurons, or smoking may alter the activity of metabolic enzymes and thus the production of toxic metabolites.

It is also possible that the same genetic or constitutional traits that raise susceptibility to PD may also deter subjects from smoking. Such traits could be a common cause for both smoking behavior and PD, Dr. Ritz and associates noted.

Tobacco's protective effect appeared to wane in subjects aged 75 and older, another finding that has been reported in previous studies. This is consistent with the hypothesis that smoking delays rather than prevents the onset of PD, the researchers added.

A pooled analysis of 11 clinical studies has confirmed that cigarette smoking protects against Parkinson's disease in a dose-dependent manner.

Many studies have suggested that smoking may play a protective role in PD, but most have been too small to provide definitive answers. Dr. Beate Ritz of the University of California, Los Angeles, and associates conducted a pooled analysis of eight case-control studies and three cohort studies involving 2,816 subjects who had PD and 8,993 controls. This large data set “enabled us to investigate aspects of cigarette smoking and subgroup-specific associations that could not be addressed adequately in previous studies,” they noted.

The risk of developing PD decreased as pack-years of cigarette smoking increased, so that the average relative risk for the disease dropped 5%–8% for every 10 pack-years of smoking. This dose-response pattern was seen in both men and women, and it was not affected by subjects' educational status.

There was also a strong dose-response trend for the number of years that had elapsed since smoking cessation. Current smokers and smokers who had recently quit showed the lowest risk for PD. People who had quit smoking in the past had a higher risk for PD, but their risk was still lower than that of people who had never smoked (Arch. Neurol. 2007;64:990–7).

Two possible mechanisms for this protective effect have been proposed. Substances such as nicotine in tobacco smoke may promote the survival of dopaminergic neurons, or smoking may alter the activity of metabolic enzymes and thus the production of toxic metabolites.

It is also possible that the same genetic or constitutional traits that raise susceptibility to PD may also deter subjects from smoking. Such traits could be a common cause for both smoking behavior and PD, Dr. Ritz and associates noted.

Tobacco's protective effect appeared to wane in subjects aged 75 and older, another finding that has been reported in previous studies. This is consistent with the hypothesis that smoking delays rather than prevents the onset of PD, the researchers added.

A pooled analysis of 11 clinical studies has confirmed that cigarette smoking protects against Parkinson's disease in a dose-dependent manner.

Many studies have suggested that smoking may play a protective role in PD, but most have been too small to provide definitive answers. Dr. Beate Ritz of the University of California, Los Angeles, and associates conducted a pooled analysis of eight case-control studies and three cohort studies involving 2,816 subjects who had PD and 8,993 controls. This large data set “enabled us to investigate aspects of cigarette smoking and subgroup-specific associations that could not be addressed adequately in previous studies,” they noted.

The risk of developing PD decreased as pack-years of cigarette smoking increased, so that the average relative risk for the disease dropped 5%–8% for every 10 pack-years of smoking. This dose-response pattern was seen in both men and women, and it was not affected by subjects' educational status.

There was also a strong dose-response trend for the number of years that had elapsed since smoking cessation. Current smokers and smokers who had recently quit showed the lowest risk for PD. People who had quit smoking in the past had a higher risk for PD, but their risk was still lower than that of people who had never smoked (Arch. Neurol. 2007;64:990–7).

Two possible mechanisms for this protective effect have been proposed. Substances such as nicotine in tobacco smoke may promote the survival of dopaminergic neurons, or smoking may alter the activity of metabolic enzymes and thus the production of toxic metabolites.

It is also possible that the same genetic or constitutional traits that raise susceptibility to PD may also deter subjects from smoking. Such traits could be a common cause for both smoking behavior and PD, Dr. Ritz and associates noted.

Tobacco's protective effect appeared to wane in subjects aged 75 and older, another finding that has been reported in previous studies. This is consistent with the hypothesis that smoking delays rather than prevents the onset of PD, the researchers added.

New prescriptions for antidepressants in children and adolescents dropped by 33% in Tennessee after regulatory agencies issued warnings about increased risks for suicide, according to Dr. Benji T. Kurian and his associates at Vanderbilt University School of Medicine, Nashville, Tenn.

The reduction was even greater for selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine and for selective norepinephrine reuptake inhibitors (SNRIs), which dropped by 54%. However, there was no cutback in already established therapy with antidepressants or other psychotropic drugs, “which suggests that the primary effect of the warnings was to alter the decision to treat newly presenting patient[s],” the researchers said.

Dr. Kurian and his associates used prescription data from TennCare, Tennessee's expanded Medicaid program, to examine prescribing trends during the 24 months preceding the 2003 regulatory warnings about antidepressants in the pediatric population and the 21 months afterward. The mean number of subjects assessed each month was 405,000.

“Previous studies have shown that trends in the pediatric use of antipsychotics in TennCare are very similar to those in the entire United States,” they noted.

Before the regulatory warnings were issued, there was a mean of 23 new antidepressant users per 10,000 children and adolescents per month, compared with 15 new users after the warnings were publicized, a decrease of 33%. The reduction in new prescriptions was most pronounced for SSRIs other than fluoxetine and for SNRIs.

In contrast, there was a 60% increase in new prescriptions for fluoxetine, the one SSRI that initially was exempted from the warnings. There was no significant change in new prescriptions for tricyclic and related antidepressants, nor in prescribing patterns for psychostimulants, mood stabilizers, antipsychotics, or benzodiazepines during this interval, the investigators said (Arch. Ped. Adoles. Med. 2007;161:690–6).

“We could not evaluate the clinical and public health consequences” of this change “because we were unable to assess the appropriateness of antidepressant prescribing in this study population,” Dr. Kurian and his associates said.

The decrease in new prescriptions may have been beneficial had the affected patients only had “marginal indications” for the drugs. “Conversely, if this group had serious affective disorders, the failure to initiate treatment could have had adverse clinical and developmental consequences,” they noted.

“There is an urgent need for better data on the efficacy and safety of antidepressants to guide pediatric practice,” Dr. Kurian and his associates said.

New prescriptions for antidepressants in children and adolescents dropped by 33% in Tennessee after regulatory agencies issued warnings about increased risks for suicide, according to Dr. Benji T. Kurian and his associates at Vanderbilt University School of Medicine, Nashville, Tenn.

The reduction was even greater for selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine and for selective norepinephrine reuptake inhibitors (SNRIs), which dropped by 54%. However, there was no cutback in already established therapy with antidepressants or other psychotropic drugs, “which suggests that the primary effect of the warnings was to alter the decision to treat newly presenting patient[s],” the researchers said.

Dr. Kurian and his associates used prescription data from TennCare, Tennessee's expanded Medicaid program, to examine prescribing trends during the 24 months preceding the 2003 regulatory warnings about antidepressants in the pediatric population and the 21 months afterward. The mean number of subjects assessed each month was 405,000.

“Previous studies have shown that trends in the pediatric use of antipsychotics in TennCare are very similar to those in the entire United States,” they noted.

Before the regulatory warnings were issued, there was a mean of 23 new antidepressant users per 10,000 children and adolescents per month, compared with 15 new users after the warnings were publicized, a decrease of 33%. The reduction in new prescriptions was most pronounced for SSRIs other than fluoxetine and for SNRIs.

In contrast, there was a 60% increase in new prescriptions for fluoxetine, the one SSRI that initially was exempted from the warnings. There was no significant change in new prescriptions for tricyclic and related antidepressants, nor in prescribing patterns for psychostimulants, mood stabilizers, antipsychotics, or benzodiazepines during this interval, the investigators said (Arch. Ped. Adoles. Med. 2007;161:690–6).

“We could not evaluate the clinical and public health consequences” of this change “because we were unable to assess the appropriateness of antidepressant prescribing in this study population,” Dr. Kurian and his associates said.

The decrease in new prescriptions may have been beneficial had the affected patients only had “marginal indications” for the drugs. “Conversely, if this group had serious affective disorders, the failure to initiate treatment could have had adverse clinical and developmental consequences,” they noted.

“There is an urgent need for better data on the efficacy and safety of antidepressants to guide pediatric practice,” Dr. Kurian and his associates said.

New prescriptions for antidepressants in children and adolescents dropped by 33% in Tennessee after regulatory agencies issued warnings about increased risks for suicide, according to Dr. Benji T. Kurian and his associates at Vanderbilt University School of Medicine, Nashville, Tenn.

The reduction was even greater for selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine and for selective norepinephrine reuptake inhibitors (SNRIs), which dropped by 54%. However, there was no cutback in already established therapy with antidepressants or other psychotropic drugs, “which suggests that the primary effect of the warnings was to alter the decision to treat newly presenting patient[s],” the researchers said.

Dr. Kurian and his associates used prescription data from TennCare, Tennessee's expanded Medicaid program, to examine prescribing trends during the 24 months preceding the 2003 regulatory warnings about antidepressants in the pediatric population and the 21 months afterward. The mean number of subjects assessed each month was 405,000.

“Previous studies have shown that trends in the pediatric use of antipsychotics in TennCare are very similar to those in the entire United States,” they noted.

Before the regulatory warnings were issued, there was a mean of 23 new antidepressant users per 10,000 children and adolescents per month, compared with 15 new users after the warnings were publicized, a decrease of 33%. The reduction in new prescriptions was most pronounced for SSRIs other than fluoxetine and for SNRIs.

In contrast, there was a 60% increase in new prescriptions for fluoxetine, the one SSRI that initially was exempted from the warnings. There was no significant change in new prescriptions for tricyclic and related antidepressants, nor in prescribing patterns for psychostimulants, mood stabilizers, antipsychotics, or benzodiazepines during this interval, the investigators said (Arch. Ped. Adoles. Med. 2007;161:690–6).

“We could not evaluate the clinical and public health consequences” of this change “because we were unable to assess the appropriateness of antidepressant prescribing in this study population,” Dr. Kurian and his associates said.

The decrease in new prescriptions may have been beneficial had the affected patients only had “marginal indications” for the drugs. “Conversely, if this group had serious affective disorders, the failure to initiate treatment could have had adverse clinical and developmental consequences,” they noted.

“There is an urgent need for better data on the efficacy and safety of antidepressants to guide pediatric practice,” Dr. Kurian and his associates said.